Exploring the Significance of Microglial Phenotypes and Morphological Diversity in Neuroinflammation and Neurodegenerative Diseases: From Mechanisms to Potential Therapeutic Targets

ABSTRACT

Studying various microglial phenotypes and their functions in neurodegenerative diseases is crucial due to the intricate nature of their phenomics and their vital immunological role. Microglia undergo substantial phenomic changes, encompassing morphological, transcriptional, and functional aspects, resulting in distinct cell types with diverse structures, functions, properties, and implications. The traditional classification of microglia as ramified, M1 (proinflammatory), or M2 (anti-inflammatory) phenotypes is overly simplistic, failing to capture the wide range of recently identified microglial phenotypes in various brain regions affected by neurodegenerative diseases. Altered and activated microglial phenotypes deviating from the typical ramified structure are significant features of many neurodegenerative conditions. Understanding the precise role of each microglial phenotype is intricate and sometimes contradictory. This review specifically focuses on elucidating recent modifications in microglial phenotypes within neurodegenerative diseases. Recognizing the heterogeneity of microglial phenotypes in diseased states can unveil novel therapeutic strategies for targeting microglia in neurodegenerative diseases. Moreover, the exploration of the use of healthy isolated microglia to mitigate disease progression has provided an innovative perspective. In conclusion, this review discusses the dynamic landscape of mysterious microglial phenotypes, emphasizing the need for a nuanced understanding to pave the way for innovative therapeutic strategies for neurodegenerative diseases.

KEYWORDS:

• Alzheimer’s disease
• microglia
• neurodegenerative diseases
• neuroinflammation
• phenotypes

Acknowledgments

We are thankful and grateful to the TWAS-UNESCO Associateship Scheme for providing MMA with a visiting research fellowship at the Department of Molecular Medicine and Bioprocesses Institute of Biotechnology, National Autonomous University of Mexico (UNAM), Av. Universidad s/n, Cuernavaca, Morelos, Mexico.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

MMA outlined the conceptual framework of the review, and wrote the first draft of the manuscript. LPM and GPA provided guidance to MMA in addressing reviewers’ comments and refining the final version of the manuscript. All the authors approved the final version of the manuscript.

Data availability statement

Data sharing is not applicable to this article as no data were analyzed in this study.